Després Jean-Pierre, Ross Robert, Boka Gabor, Alméras Natalie, Lemieux Isabelle
Québec Heart Institute, Hôpital Laval Research Centre, Université Laval, Québec, Canada.
Arterioscler Thromb Vasc Biol. 2009 Mar;29(3):416-23. doi: 10.1161/ATVBAHA.108.176362. Epub 2008 Dec 26.
Rimonabant, the first selective cannabinoid type 1 (CB1) receptor antagonist, improves cardiometabolic risk factors in overweight/obese patients. ADAGIO-Lipids assessed the effect of rimonabant on cardiometabolic risk factors and intraabdominal and liver fat.
803 abdominally obese patients with atherogenic dyslipidemia (increased triglycerides [TG] or reduced high-density lipoprotein-cholesterol [HDL-C]) were randomized to placebo or rimonabant 20 mg/d for 1 year. HDL-C and TG were coprimary end points. Intraabdominal (visceral) and liver fat were measured by computed tomography in a subgroup of 231 patients. In total, 73% of rimonabant- and 70% of placebo-treated patients completed the study treatment. Rimonabant 20 mg produced significantly greater changes from baseline versus placebo in HDL-C (+7.4%) and TG levels (-18%; P<0.0001), as well as low-density lipoprotein (LDL) and HDL particle sizes, apolipoprotein A1 and B, HDL2, HDL3, C-reactive protein, and adiponectin levels (all P<0.05). Rimonabant decreased abdominal subcutaneous adipose tissue (AT) cross-sectional area by 5.1% compared to placebo (P<0.005), with a greater reduction in visceral AT (-10.1% compared to placebo; P<0.0005), thereby reducing the ratio of visceral/subcutaneous AT (P<0.05). Rimonabant significantly reduced liver fat content (liver/spleen attenuation ratio; P<0.005). Systolic (-3.3 mm Hg) and diastolic (-2.4 mm Hg) blood pressure were significantly reduced with rimonabant versus placebo (P<0.0001). The safety profile of rimonabant was consistent with previous studies; gastrointestinal, nervous system, psychiatric, and general adverse events were more common with rimonabant 20 mg.
In abdominally obese patients with atherogenic dyslipidemia, rimonabant 20 mg significantly improved multiple cardiometabolic risk markers and induced significant reductions in both intraabdominal and liver fat.
利莫那班是首个选择性1型大麻素（CB1）受体拮抗剂，可改善超重/肥胖患者的心脏代谢危险因素。ADAGIO - 脂质研究评估了利莫那班对心脏代谢危险因素以及腹部和肝脏脂肪的影响。
803例患有致动脉粥样硬化血脂异常（甘油三酯[TG]升高或高密度脂蛋白胆固醇[HDL - C]降低）的腹型肥胖患者被随机分为安慰剂组或接受20 mg/d利莫那班治疗1年。HDL - C和TG为共同主要终点。在231例患者的亚组中通过计算机断层扫描测量腹部（内脏）和肝脏脂肪。总体而言, 73%接受利莫那班治疗的患者和70%接受安慰剂治疗的患者完成了研究治疗。与安慰剂相比，20 mg利莫那班使HDL - C（升高7.4%）和TG水平（降低18%；P<0.0001）以及低密度脂蛋白（LDL）和HDL颗粒大小、载脂蛋白A1和B、HDL2、HDL3、C反应蛋白和脂联素水平发生了显著更大的变化（均P<0.05）。与安慰剂相比，利莫那班使腹部皮下脂肪组织（AT）横截面积减少了5.1%（P<0.005），内脏AT减少幅度更大（与安慰剂相比降低10.1%；P<0.0005），从而降低了内脏/皮下AT的比例（P<0.05）。利莫那班显著降低了肝脏脂肪含量（肝脏/脾脏衰减率；P<0.005）。与安慰剂相比，利莫那班使收缩压（降低3.3 mmHg）和舒张压（降低2.4 mmHg）显著降低（P<0.0001）。利莫那班的安全性与既往研究一致；20 mg利莫那班组胃肠道、神经系统, 精神和全身不良事件更为常见。
在患有致动脉粥样硬化血脂异常的腹型肥胖患者中，20 mg利莫那班显著改善了多种心脏代谢风险指标，并使腹部和肝脏脂肪显著减少。
